Methanol → 6-Methoxy-10-(4-methoxy-phenyl)-1,2,3,4,4a,10a-hexahydro-phenanthren-9-carboxylic acid methyl ester

HRID 418943Notes

Reaction equation

HRID 418943 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:14](=[CH:15][CH:16]=1)[C:13](OS(C(F)(F)F)(=O)=O)=[C:12]([C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=1)[CH:11]1[CH:6]2[CH2:7][CH2:8][CH2:9][CH2:10]1.C1C=CC(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC.CO.[C:72]([O:75][CH2:76]C)(=[O:74])C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CS(C)=O>[CH3:76][O:75][C:72]([C:13]1[C:14]2[C:5]([CH:6]3[CH:11]([C:12]=1[C:25]1[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=1)[CH2:10][CH2:9][CH2:8][CH2:7]3)=[CH:4][C:3]([O:2][CH3:1])=[CH:16][CH:15]=2)=[O:74]

Participants

8

Reactant 5

HCID 887MethanolHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 821241,4-Bis(diphenylphosphino)butaneHCID 72309400Trifluoro-methanesulfonic acid 6-methoxy-10-(4-methoxy-phenyl)-1,2,3,4,4a,10a-hexahydro-phenanthren-9-yl ester

Product 1

HCID 666519606-Methoxy-10-(4-methoxy-phenyl)-1,2,3,4,4a,10a-hexahydro-phenanthren-9-carboxylic acid methyl esterYield 63%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

Combine trifluoro-methanesulfonic acid 6-methoxy-10-(4-methoxy-phenyl)-1,2,3,4,4a,10a-hexahydro-phenanthren-9-yl ester (19.83 g, 42.3 mmol), palladium acetate (1.93 g), dppb (4.58 g), Et3N (60.0 mL), methanol (265 mL), and DMSO (400.0 mL), and stir under 100 psi of CO atmosphere at 80° C. After 18 hours, add ethyl acetate and wash the ethyl acetate 5× with brine, then dry the organic phase with anhydrous sodium sulfate and concentrate. Flash chromatograph using 5% to 30% ethyl acetate/hexanes to yield the titled compound (10.06 g, 63%) as a pinkish-white solid. TLC Rf=0.25 in 6:1 hexanes:ethyl acetate. 1H NMR (CDCl3): 7.31 (m, 2H), 7.25 (d, 1H, J=8.4 Hz), 6.92 (m, 3H), 6.76 (dd, 1H, J=8.6, 2.4 Hz), 3.86 (m, 6H), 3.60 (s, 3H), 3.25 (d, 1H, J=4.4 Hz), 2.70 (m, 1H), 2.40 (m, 1H), 1.75 (m, 1H), 1.53 (m, 4H), 1.31 (m, 2H).

Workup

  1. washwash the ethyl acetate 5× with brine
  2. dry with materialdry the organic phase with anhydrous sodium sulfate
  3. concentrationconcentrate

Sources & evidence

ORD record
ord-f9ba617e1fb6427792990d3eed129837
Source dataset
uspto-grants-2012_01
Patent number
US08093302B2

Reaction notes

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